This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is directed at five specific aims: D.1: The synthesis of gnidimacrin, a potent lead for the treatment of cancer based on PKC targeting;D.2: The development of a general and flexible rout to anticancer leads in the daphnane family and study of their activity;D.3: The synthesis and biological evaluation of daphnane-tigliane hybrids; D.4: The synthesis and biological evaluation of laulimalide analogs, compounds active against taxol resistant cancers; D.5: The design, synthesis, and evaluation of drug and probe transporters involving a real time bioluminescence assay with a specific focus on transporter conjugates that are designed for selective cell or tissue entry based on activation by extracellular proteases.